Injuries to bone, such as partial or complete fracture, can be slow to heal, but such injuries generally heal on their own accord with external immobilization as needed, such as by applying a cast to the affected area. In more severe cases, more aggressive internal immobilization, such as permanently reconnecting the fractured bone with screws and/or metal plates, may be required. Regeneration of bone tissue over the relatively short distances generally present in bone fracture readily occurs in most healthy patients. Bone injuries beyond simple fractures, however, present greater challenges in treatment. Long segmental diaphyseal bone loss, for example, can result from multiple causes including high-energy trauma, such as blast injury, disease, such as osteomyelitis or osteonecrosis, or wide excision of malignant conditions, such as osteosarcoma. Such conditions often result in cavitation of the bone or complete loss of bone tissue across an extended length of the bone (i.e., a critical bone defect). Bone regeneration in these cases becomes increasingly challenging and sometimes impossible.
Many techniques have been used in an attempt to enhance bone growth. Most commonly, an attempt is made to replace the lost bone. Examples of such techniques include autologous vascularized bone grafts, massive allograft (generally from cadaver), and use of reabsorbable and non-reabsorbable artificial bone. Another method for promoting bone regeneration is through the introduction of osteoinductive bioactive factors, such as bone morphogenetic proteins (BMPs), platelet rich plasma (PRP), synthetic peptides, such as P-15 (Pepgen P-15™, Dentsply International, York, Pa.), and bone marrow aspirates. Such bioactive factors can be introduced into the area of bone loss through various vehicles. Mechanical methods, such as distraction osteogenesis, are also employed for promoting bone regeneration. Distraction osteogenesis is a process involving gradual, controlled displacement of surgically created fractures resulting in simultaneous expansion of soft tissue and bone volume.
A somewhat less invasive technique that is used most commonly for regenerating bone around teeth is known as “guided bone regeneration.” As the tissue surrounding a bone almost always heals faster than the bone itself, the faster-healing tissue often expands into and fills the space where the bone is missing, hindering the bone regeneration. In guided bone regeneration, a biocompatible membrane is placed between the tissue and the bone acting as a barrier, which prevents growth of the tissue into the bone. Often, a bone graft is inserted under the barrier. The membranes are typically designed to dissolve away after several weeks.
A variation on this procedure is known as “protected bone regeneration” and is based on the theory that three prerequisites for bone healing are required: 1) adequate blood supply, 2) abundant bone forming cells, and 3) protected healing space. See, Holmes, R. E., Lemperle, S. M., and Calhoun, C. J., “Protected Bone Regeneration,” Scientific Data Series in Resorbable Fixation, distributed by Medtronic Sofamor Danek, available on-line at http://www.macropore.com/pdf/Protected_Bone.pdf. Adequate blood supply is a known requirement for bone regeneration as it supplies the necessary oxygen and nutrients, as well as mesenchymal stem cells (the bone forming cells). As described above, the healing space of the bone must also be protected from the ingrowth of surrounding tissue. According to the above-noted publication, all of the stated prerequisites can be met through the use of a reabsorbable polymer protective sheet offering a physiologically balanced porosity for positive cellular exchange and the opportunity for vascular infiltration, while preventing interposition of adjacent soft tissues.
While there are several methods currently known, treatment of injury resulting in major bone loss remains a difficult clinical problem. Furthermore, approximately 10% of all long bone fractures are non-union fractures that do not heal spontaneously. Thus, there remains a need for methods for bone regeneration that are effective at promoting bone tissue growth and that are as non-invasive as possible.